Amino-tetrahydronaphthalene derivatives

ABSTRACT

The invention relates to aminotetrahydronaphthalene derivatives which are intermediates for the preparation of sulfonylaminotetrahydronaphthalenes.

This application is a divisional of copending application Ser. No.07/605,433, filed on Oct. 30, 1990. The entire contents of which arehereby incorporated by reference.

FIELD OF THE INVENTION

This invention relates to novel tetrahydronaphthalene derivatives,processes for preparation thereof and intermediates therefor.

PRIOR ART

Thromboxan A₂ (hereinafter, referred to as "TxA₂ ") is a metabolite ofarachidonic acid which exists widely in various organs of animals (e.g.liver, kidney, lung, brain, etc.). TxA₂ is known to show plateletaggregation activity and induces a variety of thrombosis such asperipheral vascular thrombosis, pulmonary embolism, coronary arterythrombosis, myocardial infarction, transient ischemia, and the like.Therefore, 2-benzenesulfonylaminoethyl derivatives of phenoxyacetic acidor tetrahydronaphthyloxyacetic acid which have TxA₂ -antagonisticactivity have been suggested to be useful in the therapeutic treatmentof these diseases (cf. Thrombosis Research, 35, 379-395, 1984, U.S. Pat.No. 4,868,331).

SUMMARY DESCRIPTION OF THE INVENTION

As a result of various investigation, there have been found noveltetrahydronaphthalene derivatives which show stronger TxA₂ antagonisticactivity as compared with the above known compounds.

Thus, the objects of the invention are to provide noveltetrahydronaphthalene derivatives and a pharmaceutical compositioncontaining the same. Another object of the invention is to provideprocesses for preparing said compounds. A further object of theinvention is to provide novel intermediates which are useful in thesynthesis of the tetrahydronaphthalene derivatives of the invention.These and other objects and advantages of the invention will be apparentto those skilled in the art from the following description.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to a tetrahydronaphthalene derivative of theformula: ##STR1## wherein R¹ is a substituted or unsubstituted phenylgroup, naphthyl group, a sulfur- or nitrogen-containing heterocyclicgroup, a lower alkyl group or cycloalkyl group, and R² is hydroxymethylgroup, carboxyl group, a lower alkoxycarbonyl group or a group of theformula: ##STR2## wherein R³ is hydrogen atom or a lower alkyl group, R⁴is a lower alkoxycarbonyl-phenyl group, carboxy-phenyl group, a loweralkyl group, a lower alkoxycarbonyl-lower alkyl group or carboxy-loweralkyl group, and m and n are different and are integers of 1 and 2, or apharmaceutically acceptable salt thereof.

Said tetrahydronaphthalene derivative of the invention or a salt thereofshow potent TxA₂ antagonistic and/or platelet aggregation-inhibitingactivities and are useful for the therapeutic treatment, ameliorationand/or prophylaxis of a variety of thrombosis or embolism, coronary andcerebral vascular smooth muscle vellication, asthma, and the like.

Examples of the novel tetrahydronaphthalene derivative of the inventionare those of the formula (II) wherein R¹ is a phenyl group, a loweralkylphenyl group, a lower alkoxyphenyl group, a halogenophenyl group,naphthyl group, thienyl group, pyridyl group, a lower alkyl group orcycloalkyl group.

Preferred examples of the compound of the invention are those of theformula (I) wherein R² is a hydroxymethyl group, carboxyl group, or agroup of the formula: ##STR3## wherein R³ is hydrogen atom and R⁴ is acarboxy-lower alkyl group.

Preferred examples of the compound of the invention are also those ofthe formula (I) wherein m is 1 and n is 2.

More preferred examples of the compound of the invention are those ofthe formula (I) wherein R¹ is a phenyl group, methylphenyl group,methoxyphenyl group, chlorophenyl group, thienyl group, methyl group orcyclohexyl group, and R² is a carboxyl group or a group of the formula:##STR4## wherein R³ is a hydrogen atom and R⁴ is a carboxy-lower alkylgroup.

Most preferred examples of the compounds of the invention are those ofthe formula (I) wherein R¹ is a chlorophenyl group, and R² is a group ofthe formula: ##STR5## wherein R³ is a hydrogen atom and R⁴ is acarboxyethyl group or carboxypropyl group.

In the above-mentioned examples of the tetrahydronaphthalene derivative(I), the lower alkyl group, the lower alkoxy group and the cycloalkylgroup include an alkyl group of one to six carbon atoms, an alkoxy groupof one to six carbon atoms and cycloalkyl group of three to six carbonatoms, respectively. Preferred examples of these groups are an alkylgroup of one to four carbon atoms, an alkoxy group of one to four carbonatoms and cycloalkyl group of five to six carbon atoms, respectively.Examples of the sulfur- or nitrogen-containing heterocyclic group aresulfur- or nitrogen-containing 5- or 6-membered heteromonocyclic groupssuch as thienyl or pyridyl groups.

The compounds (I) of the invention may exist in the form of twooptically active isomers due to one asymmetric carbon atom, and thisinvention includes these optically active isomers and a mixture thereof.

According to this invention, the compound (I) or salts thereof can beprepared by condensing an aminotetrahydronaphthalene derivative of theformula: ##STR6## wherein R², m and n are as defined above, or a saltthereof with a sulfonic acid compound of the formula:

    R.sup.1 SO.sub.3 H                                         (III)

wherein R¹ is a as defined above, or a reactive derivative thereof.

The compound of the formula (I) wherein R² is hydroxymethyl group, i.e.the compounds of the formula (I-a): ##STR7## wherein R¹, m and n are asdefined above, can also be prepared by reducing a compound of theformula (I-b): ##STR8## wherein R¹, m and n are as defined above.

On the other hand, the compounds of the formula (I) wherein R² is agroup of the formula: ##STR9## i.e. the compounds of the formula (I-c):##STR10## wherein R¹, R³, R⁴, m and n are as defined above may beprepared by condensing a compound of the formula (I-b) or a reactivederivative at carboxyl group thereof with an amine compound of theformula:

    R.sup.3 --NH--R.sup.4                                      (IV)

wherein R³ and R⁴ are as defined above, or a salt thereof.

Moreover, the compounds of the formula (I) wherein R² is a group of theformula: ##STR11## i.e. the compounds of the formula (I-d): ##STR12##wherein R⁵ is carboxy-phenyl group or a carboxy-lower alkyl group, andR¹, R³, m and n are as defined above, may be prepared by hydrolyzing acompound of the formula (I-e): ##STR13## wherein R⁶ is a loweralkoxycarbonyl-phenyl group or a lower alkoxycarbonyl-lower alkyl group,and R¹, R³, m and n are as defined above.

The condensation reaction of the aminotetrahydronaphthalene (II) or asalt thereof with the sulfonic acid compound (III) or a reactivederivative thereof can be carried out in the presence or absence of anacid acceptor. The reactive derivative of the compound (III) includesany conventional reactive derivatives, for example, the correspondingsulfonyl halide. The acid acceptor includes any conventional agents, forexample, alkali metal carbonates, alkali metal hydrogen carbonates,trialkylamines, pyridine, and the like. Examples of the salt of thestarting compound (II) include mineral acid salts (e.g., hydrochloride,sulfate, etc.), organic acid salts (e.g., methanesulfonate,p-toluenesulfonate, dibenzoyltartrate etc.), and so forth. The reactionis preferably carried out in a suitable solvent (e.g. water, ethylacetate) at a temperature of 0° to 200° C.

The reduction of the compound (I-b) can be carried out by treating itwith a reducing agent. The reducing agent includes, for example, borane1,4-oxathiane complex. This reduction is preferably carried out in anappropriate solvent (e.g. ether tetrahydrofuran) at a temperature of 0°to 50° C.

The condensation reaction of the compound (I-b) or a reactive derivativeat carboxyl group thereof with the amine compound (IV) can be carriedout by any conventional method. For example, the condensation reactionof the free carboxylic acid (I-b) and the compound (IV) can be carriedout in the presence of a dehydrating agent. The dehydrating agentincludes, for example, carbonyldiimidazole, dicyclohexylcarbodiimide,and the like. Besides, the condensation reaction of the reactivederivative at carboxyl group of the compound (I-b) with the aminecompound (IV) can be carried out in the presence or absence of an acidacceptor. A variety of the reactive derivative at the carboxyl group ofthe compound (I-b), including, for example, acid halides, activatedesters may be used for the condensation reaction. The acid acceptorincludes alkali metal carbonates, alkali metal hydrogen carbonates,trialkylamines, pyridine, and the like. These reactions are preferablycarried out in an appropriate solvent (e.g. tetrahydrofuran, methylenechloride, ethyl acetate) at a temperature of 0° to 50° C.

The hydrolysis of the compound (I-e) can be carried out by conventionalmethod, for example, by treating the compound with an alkali agent or anacid. Examples of the alkali agent are alkali metal hydroxides, andexamples of the acid are mineral acids. The hydrolysis is preferablycarried out in an appropriate solvent (e.g. water, a lower alkanol) at atemperature of 0° to 30° C.

All of the above reactions proceed without racemization, and hence, whenan optically active compounds are used as the starting compounds, thedesired compounds (I) can be obtained in the optically active form.

The compounds (I) of this invention can be used for pharmaceutical useeither in the free form or a pharmaceutically acceptable salt. Examplesof the pharmaceutically acceptable salts include inorganic or organicsalts such as alkali metal salts (e.g. sodium salt, potassium salt),alkaline earth metal salts (e.g. calcium salt, magnesium salt), heavymetal salts (e.g. zinc salt), ammonium salt, organic amine salts (e.g.triethylamine salt, pyridine salt, ethanolamine salt, a basic amino acidsalt), and the like. These salts may readily be prepared by treating thecompounds (I) with the corresponding inorganic or organic base in anappropriate solvent.

The compounds (I) or a salt thereof may be administered either orally orparenterally to a warm-blooded animal, including human beings, and mayalso be used in the form of a pharmaceutical preparation containing thesame compound in admixture with pharmaceutical excipients suitable fororal or parenteral administration. The pharmaceutical preparations maybe in solid form such as tablets, capsules and powders, or in liquidform such as solutions, suspensions or emulsions. Moreover, whenadministered parenterally, it may be used in the form of injections.

Because of the potent TxA₂ antagonistic activity, the compound (I) ofthe invention or a salt thereof are useful as plateletaggregation-inhibiting agent and for the treatment, amelioration and/orprophylaxis of a variety of thrombosis or embolism, such as cerebralthrombosis, coronary artery thrombosis, pulmonary thrombosis, pulmonaryembolism, peripheral vascular embolism, thromboangiitis, and the like.The compound (I) or a salt thereof are also useful for prophylaxis of i)thrombosis which may be caused during extracorporeal circulation ofblood and ii) thrombosis in case of an organ transplantation.

Moreover, based on the potent TxA₂ antagonistic activity, the compound(I) or a salt thereof may be used for the treatment, amelioration and/orprophylaxis of myocardial ischemia, unstable angina pectoris, coronaryvellication, cerebral blood vessel vellication after subarachnoidhemorrhage, cerebral hemorrhage, asthma, nephritis, renal failure, ashock, and the like. Besides, as some known TxA₂ antagonists showexcellent TxA₂ antagonistic activity but at the same time show transientTxA₂ -like activity, they are liable to side effects such as plateletaggregation-inducing activity, broncho-constriction activity, bloodvessel construction activity. As compared with the known antagonists,however, the compound (I) of this invention is quite advantageous foruse by either oral or parenteral administration because it issubstantially free from such TxA₂ -like activity.

Concomitantly, the starting compound (II) wherein m is 1 and R² is alower alkoxycarbonyl group can be prepared, for example, by the steps ofreacting an acid chloride of mono(a lower alkyl) 1,4-phenylenediaceticacid with ethylene to give a lower alkyl6-oxo-5,6,7,8-tetrahydronaphthalene-2-acetate, and reacting the productwith methoxylamine to give ethyl6-methoxyimino-5,6,7,8-tetrahydronaphthalene-2-acetate (V), followed bya catalytic reduction.

On the other hand, the starting compound (II) wherein m is 2 and R² is alower alkoxycarbonyl group can be prepared, for example, by hydrolysisof ethyl 7-methoxycarbonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate,followed by treating the product with a lower alkanol.

The starting compound (II) wherein R² is carboxyl group can be prepared,for example, by hydrolysis of the corresponding compound (II) wherein R²is a lower alkoxycarbonyl group, and may be, if required, furthercondensed with the amine compound (IV) to give the compound (II) whereinR² is a group of the formula: ##STR14## wherein R³ and R⁴ are as definedabove.

The compound (II) wherein R² is hydroxymethyl group can be prepared byreducing the compound (II) wherein R² is carboxyl group or a loweralkoxycarbonyl group or by reducing the compound (V) by using boranemethylsulfide complex.

EXPERIMENT Effect on U-46619-induced Platelet Aggregation (In vitro)

Nine volumes of blood collected from a healthy human were mixed with onevolume of 3.8% (w/v) trisodium citrate solution, and the mixture wascentrifuged to give platelet-rich plasma ("PRP") as the supernatant. Thebottom layer was further centrifuged to give platelet-poor plasma("PPP") as the supernatant. PRP was diluted with PPP so that theplatelet count was 4×10⁵ cells/mm³. 25 μl of a test compound solutionwas added to 200 μl of said diluted PRP. After the mixture was stirredfor 2 minutes at 37° C., U-46619 solution (0.2 μg/ml solution) was addedthereto to induce platelet aggregation. The degree of plateletaggregation was examined by Born's method (Nature, 194, 927 (1962)), andthe platelet aggregation-inhibiting activity of the test compound wasestimated. The platelet aggregation-inhibiting activity of the testcompound expressed as IC₅₀, i.e., the concentration of the test compoundrequired to induce 50% inhibition of U-46619-induced plateletaggregation. The results are shown in the following Table 1 .

                  TABLE 1                                                         ______________________________________                                        U-46619-induced platelet aggregation-inhibiting activity (in vitro)           Test                                                                          Compounds*)     IC.sub.50 (μg/ml)                                          ______________________________________                                        (the compounds of the present invention)                                      Compound No. 1  0.2                                                           Compound No. 2  0.06                                                          Compound No. 3  0.7                                                           ______________________________________                                         *) note: chemical name of each test compound:                                 Compound No. 1  Sodium                                                        3{[6(4-methylphenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-yl]acet    laminon-propionate                                                             Compound No. 2  Sodium                                                        6(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate        Compound No. 3  Sodium                                                        4{[6(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-yl]acet    laminon-butyrate                                                          

EXAMPLE 1

A solution of 1.94 g of 4-chlorophenylsulfonyl chloride in 20 ml ofethyl acetate is added to a mixture of 30 ml of ethyl acetate, 20 ml ofwater, 3.46 g of potassium carbonate and 2.25 g of ethyl6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate hydrochloride understirring at room temperature. After the mixture is stirred at roomtemperature for 45 minutes, the organic layer is separated therefrom,washed, dried and evaporated to remove the solvent. The residue ispurified by silica gel column chromatography (solvent; chloroform) togive 2.84 g of ethyl6-(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetateas oil.

Yield 83%

Mass(m/z): 408 (M⁺ +1)

IR ν_(max) ^(neat) (cm⁻¹): 3280, 1730, 1160

EXAMPLES 2 TO 15

The corresponding starting compounds are treated in the same manner asdescribed in Example 1 to give the compounds shown in Tables 2 to 4.

                  TABLE 2                                                         ______________________________________                                         Ex.                                                                                ##STR15##                                                               No.  R.sup.1        Physical properties                                       ______________________________________                                              ##STR16##     oil MS(m/z): 374(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3270, 1730, 1160                                    3                                                                                   ##STR17##     oil MS(m/z): 388(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3270, 1730, 1160                                    4                                                                                   ##STR18##     oil MS(m/z): 380(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3280, 1730, 1160                                    5                                                                                   ##STR19##     oil MS(m/z): 380(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3280, 1730, 1140                                    6    CH.sub.3       m.p. 108.5-110° C.*.sup.1                                              MS(m/z): 311(M.sup.+)                                                         IRν.sub.max.sup.neat cm-1: 3260, 1740, 1150            7    (CH.sub. 2).sub.3 CH.sub.3                                                                   oil                                                                           MS(m/z): 353(M.sup.+)                                                         IRν.sub.max.sup.neat cm-1: 3280, 1730,                 ______________________________________                                                            1150                                                       *.sup.1 recrystallized from ethyl acetate and nhexane (same as in the         following Examples)                                                      

                  TABLE 3                                                         ______________________________________                                         Ex.                                                                                ##STR20##                                                               No.  R.sup.1        Physical properties                                       ______________________________________                                         8                                                                                  ##STR21##     oil MS(m/z): 394(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3270, 1730, 1150                                     9                                                                                  ##STR22##     oil MS(m/z): 390(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3280, 1735                                          10                                                                                  ##STR23##     oil MS(m/z): 410(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3280, 1735                                          11                                                                                  ##STR24##     oil MS(m/z): 361(M.sup.+ +1) IRν.sub.max.sup.neat                          cm-1: 3270, 1740                                          12   CH.sub.3       oil                                                                           MS(m/z): 298(M.sup.+ +1)                                                      IRν.sub.max.sup.neat cm-1: 3280, 1735                  13   (CH.sub.2).sub.3 CH.sub.3                                                                    oil                                                                           MS(m/z): 339(M.sup.+ +1)                                                      IRν.sub.max.sup.neat cm-1: 3280,                       ______________________________________                                                            1735                                                  

                  TABLE 4                                                         ______________________________________                                         Ex.                                                                                 ##STR25##                                                              No.   R.sup.1       Physical properties                                       ______________________________________                                        14                                                                                   ##STR26##    colorless oil MS(m/z): 332(M.sup.+ +1) IRν.sub.max.                        sup.neat cm-1: 3500, 3280, 1160                           15                                                                                   ##STR27##                                                                                   ##STR28##                                                ______________________________________                                    

EXAMPLE 16

(1) 8.29 g of potassium carbonate and 60 ml of ethyl acetate are addedto 4.05 g of ethyl 6-amino-5,6,7,8-tetrahydronaphthalene-2-acetatehydrochloride, and 30 ml of water are added thereto under cooling andstirring. After the mixture is stirred at room temperature for 10minutes, the organic layer is separated therefrom, dried and evaporatedto remove the solvent to give 3.16 g of oil product. A solution of 5.64g of (+)-D-dibenzoyltartaric acid in 50 ml of ethanol is added to asolution of the oil obtained above in 50 ml of ethanol. The precipitatedcrystals are collected and recrystallized from a mixture of ethanol andwater to give 2.10 g of ethyl(+)-6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate 1/2(+)-D-dibenzoyltartrate as colorless prism.

Yield 34%

m.p. 216°-217° C. (decomp.)

The mother liquid is evaporated to remove the solvent, and 30 ml ofwater, 8.29 g of potassium carbonate and 60 ml of ethyl acetate areadded thereto. The organic layer is separated from the solution, driedand evaporated to remove the solvent to give 1.86 g of oil product. Asolution of 3.32 g of (-)-L-dibenzoyltartaric acid in 50 ml of ethanolis added to a solution of the oil obtained above in 40 ml of ethanol.The precipitated crystals are collected and recrystallized from amixture of ethanol and water to give 1.79 g of ethyl(-)-6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate 1/2(-)-L-dibenzoyltartrate as colorless prism.

Yield 29%

m.p. 214°-215° C. (decomp.)

(2) 2.99 g of potassium carbonate, 20 ml of ethyl acetate and 40 ml ofwater are added to 2.09 g of ethyl(+)-6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate 1/2(+)-D-dibenzoyltartrate, and a solution of 1.28 g of 4-chlorophenylsulfonyl chloride in 20 ml of ethyl acetate is addedthereto at room temperature under stirring. After the mixture is stirredat room temperature for 1.5 hour, the organic layer is separatedtherefrom, washed, dried and evaporated to revove the solvent. Theresidue is purified by silica gel column chromatography (solvent;chloroform) to give 2.10 g of ethyl(+)-6-(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetateas colorless viscous oil.

[α]_(D) ²⁰ +44.6.(c=1.20, chloroform)

Ethyl (-)-6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate 1/2(-)-L-dibenzoyltartrate is treated in the same manner as described aboveto give ethyl(-)-6-(4chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetateas colorless viscous oil.

[α]_(D) ²⁰ -45.2.(c=1.47, chloroform)

EXAMPLE 17

28 ml of ethanol and 10 ml of a 2N aqueous sodium hydroxide solution areadded to 2.81 g of ethyl6-(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate,and the mixture is stirred at room temperature overnight. After ethanolis removed from the mixture, water is added thereto, and the mixture iswashed with methylene chloride. 10% hydrochloric acid is added to thewater layer, and the mixture is extracted with ethyl acetate. Theextract is washed, dried and evaporated to remove the solvent, and theresidue is recrystallized from a mixture of ethyl acetate and n-hexaneto give 2.16 g of6-(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-aceticacid as pale brown prism.

Yield 82%

m.p. 152°-154.5° C.

Mass(m/z): 380(M⁺ +1)

IR ν_(max) ^(nujol) (cm⁻¹): 3240, 1710, 1330, 1160

Sodium salt: pale brown powder

FABMass(m/z): 424, 402(M⁺ +1)

IR ν_(max) ^(nujol) (cm⁻¹): 1580, 1380

EXAMPLES 18 to 31

The corresponding starting compounds are treated in the same manner asdescribed in Example 17 to give the compounds shown in Tables 5 to 6.

                  TABLE 5                                                         ______________________________________                                         Ex.                                                                                ##STR29##                                                               No.  R.sup.1       Physical properties                                        ______________________________________                                        18                                                                                  ##STR30##    m.p. 127-128.5° C.*.sup.1 MS(m/z): 346(M.sup.+                         +1) IRν.sub.max.sup.nujol cm-1: 3300, 1700 Sodium                          salt: amorphous FABMS(m/z): 390, 368(M.sup.+ +1)                              IRν.sub.max.sup.nujol cm-1: 3260, 1570, 1460            19                                                                                  ##STR31##    m.p. 160.5-162° C.*.sup.1 MS(m/z): 360(M.sup.+                         +1) IRν.sub.max.sup.nujol cm-1: 3280, 1700 Sodium                          salt: amorphous FABMS(m/z): 404, 382(M.sup.+ +1)                              IRν.sub.max.sup.nujol cm-1: 3260, 1570, 1460            20                                                                                  ##STR32##    m.p. 143-145° C.*.sup.1 MS(m/z): 352(M.sup.+                           +1) IRν.sub.max.sup.nujol cm-1: 3290, 1700, 1330                           Sodium salt: amorphous FABMS(m/z): 396, 374(M.sup.+                           +1)                                                                           IRν.sub.max.sup.nujol cm-1: 3260, 1570, 1380            21                                                                                  ##STR33##    m.p. 163-164° C.*.sup.2 MS(m/z): 352(M.sup.+                           +1) IRν.sub.max.sup.nujol cm-1: 3280, 1690, 1320                           Sodium salt: amorphous FABMS(m/z): 396, 374(M.sup.+                           +1)                                                                           IRν.sub.max.sup.nujol cm-1: 3280, 1570, 1380            22                                                                                  ##STR34##    m.p. 163-164° C.*.sup.1 MS(m/z): 379(M.sup.+)                          IRν.sub.max.sup.nujol cm-1: 3250, 1710, 1700, 1330,                        1150 [α].sub.D.sup.20 +53.8°(c=1.86,                             ethyl acetate) Sodium salt: colorless powder                                  FABMS(m/z): 424, 402(M.sup.+ +1)                                              IRν.sub.max.sup.nujol cm-1: 1580, 1380                                     [α].sub.D.sup.20 +47.5°(c=1.03,                                  methanol)                                                  23                                                                                  ##STR35##    m.p. 162.5-164° C.*.sup.1 MS(m/z): 379(M.sup.+)                        Rν.sub.max.sup.nujol cm-1: 3250, 1710, 1700, 1330,                         1150 [α].sub.D.sup.20 -53.9°(c=1.02,                             ethyl acetate) Sodium salt: colorless powder                                  FABMS(m/z): 424, 402(M.sup.+ +1)                                              IRν.sub.max.sup.nujol cm-1: 1580, 1380                                     [α].sub.D.sup.20 -48.1°(c=0.906,                                 methanol)                                                  24   CH.sub.3      m.p. 162.5-164° C.*.sup.2                                              MS(m/z): 283(M.sup.+)                                                         IRν.sub.max.sup.nujol cm-1: 3280, 1700, 1150                               Sodium salt:                                                                  210-212° C. (dec.)*.sup.3                                              FABMS(m/z): 328, 306(M.sup.+ +1)                                              IRν.sub.max.sup.nujol cm-1: 3550, 1580                  25   (CH.sub.2).sub.3 CH.sub.3                                                                   m.p. 128-129.5° C.*.sup.1                                              MS(m/z): 325(M.sup.+)                                                         IRν.sub.max.sup.nujol cm-1: 3290, 3250, 1700                               Sodium salt:                                                                  188-190° C. (dec.)*.sup.3                                              FABMS(m/z): 370, 348(M.sup.+ +1)                                              IRν.sub.max.sup.nujol cm-1: 3260,                       ______________________________________                                                           1560                                                        *.sup. 2 recrystallized from nhexane, tetrahydrofuran and isopropyl ether     *.sup.3 recrystallized from water and isopropyl alcohol (same as in the       following Examples)                                                      

                  TABLE 6                                                         ______________________________________                                         Ex.                                                                                ##STR36##                                                               No.  R.sup.1        Physical properties                                       ______________________________________                                        26                                                                                  ##STR37##     m.p. 130-133° C.*.sup.1 MS(m/z): 380(M.sup.+                           +1) IRν.sub.max.sup.nujol cm-1: 3320, 3150, 1710                           Sodium salt: amorphous FABMS(m/z): 424, 402(M.sup.+                           +1)                                                                           IRν.sub.max.sup.nujol cm-1: 3260, 1570, 1385           27                                                                                  ##STR38##     m.p. 121-123° C.*.sup.1 MS(m/z): 376(M.sup.+                           +1) IRν.sub.max.sup.nujol cm-1: 3320, 3250, 1720                           Sodium salt: m.p. 195-197° C.*.sup.3               28                                                                                  ##STR39##     m.p. 184-186° C.*.sup.1 MS(m/z): 396(M.sup.+                           +1) IRν.sub.max.sup.nujol cm-1: 3350, 3240, 1720                           Sodium salt: m.p. 137-144° C.*.sup.3               29                                                                                  ##STR40##     m.p. 174-177° C.*.sup.1 MS(m/z): 347(M.sup.+                           +1) IRν.sub.max.sup.nujol cm-1: 3300, 2500, 1710                           Sodium salt: m.p. 203-205° C.*.sup.3               30   CH.sub.3       m.p. 136.5-137.5° C.*.sup.1                                            MS(m/z): 283(M.sup.+ +1)                                                      IRν.sub.max.sup.nujol cm-1: 3270, 1690                                     Sodium salt:                                                                  m.p. 267-269° C. (dec.)*.sup.3                     31   (CH.sub.2).sub.3 CH.sub.3                                                                    m.p. 113-113.5° C.*.sup.1                                              FABMS(m/z): 326(M.sup.+ +1)                                                   IRν.sub.max.sup.nujol cm-1: 3280, 1690                                     Sodium salt:                                                                  m.p. 208-210° C.*.sup.3                            ______________________________________                                    

EXAMPLE 32

A mixture of 1.51 g of6-(2-thienyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetic acid,20 ml of methylene chloride, one drop of dimethylformamide and 3.3 ml ofthionyl chloride is refluxed for 2 hours, and the solvent is removed togive yellow oil. A solution of the oil in 20 ml of methylene chloride isadded dropwise to a solution of 1.30 g of methyl 4-aminobenzoate and1.31 g of triethylamine in 15 ml of methylene chloride under stirring atroom temperature. After the mixture is stirred overnight, the solvent isdistilled off. Ethyl acetate and 10% hydrochloric acid are added to theresidue, and the organic layer is separated therefrom, washed, dried andevaporated to remove the solvent. The resulting solid is recrystallizedfrom a mixture of tetrahydrofuran and isopropyl ether to give 1.58 g ofmethyl4-{[6-(2-thienyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-yl]acetylamino}benzoateas pale yellow crystals.

Yield 76%

m.p. 210°-212° C.

FABMass(m/z): 485(M⁺ +1)

IR ν_(max) ^(nujol) (cm⁻¹): 3320, 3230, 1710, 1690, 1150

EXAMPLES 33 to 45

The corresponding starting compounds are treated in the same manner asdescribed in Example 32 to give the compounds shown in Tables 7 to 8.

                  TABLE 7                                                         ______________________________________                                         Ex.                                                                                ##STR41##                                                               No.  R.sup.1       q      Physical properties                                 ______________________________________                                        33                                                                                  ##STR42##    2      m.p. 131.5-132.5° C.*.sup.1 MS(m/z):                                   445(M.sup.+ +1) IRν.sub.max.sup.nujol cm-1:                                3320, 3180, 1735, 1665, 1150                        34                                                                                  ##STR43##    3      m.p. 144-145° C.*.sup.4 MS(m/z):                                       479(M.sup.+ +1) IRν.sub.max.sup.nujol cm-1:                                3340, 3160, 1730, 1660, 1160                        35                                                                                  ##STR44##    2      m.p. 170-171° C.*.sup.1 MS(m/z):                                       465(M.sup.+ +1) IRν.sub.max.sup.nujol cm-1:                                3320, 3160, 1740, 1660, 1550                        36                                                                                  ##STR45##    1      m.p. 153-154° C.*.sup.4 MS(m/z):                                       450(M.sup.+) IRν .sub.max.sup.nujol cm-1:                                  3350, 3180, 1750, 1660, 1160                        37                                                                                  ##STR46##    3      m.p. 105-107° C.*.sup.1 MS(m/z):                                       450(M.sup.+) IRν.sub.max.sup.nujol cm-1:                                   3340, 3140, 1735, 1660, 1540                        38                                                                                  ##STR47##    3      m.p. 111-113° C.*.sup.4 [α].sub.D.s                              up.20 +46.8°(c=2.38, methanol)               39                                                                                  ##STR48##    3      m.p. 110-112° C.*.sup.4 [α].sub.D.s                              up.20 -47.3°(c=2.22, methanol)               40                                                                                  ##STR49##    2      m.p. 132-134° C.*.sup.4 [α].sub.D.s                              up.20 +44.4°(c=1.17, tetrahydrofuran)        41                                                                                  ##STR50##    2      m.p. 132-133.5° C.*.sup.4 [α].sub.D                              .sup.20 -44.2°(c= 1.05, tetrahydrofuran)     ______________________________________                                         *.sup.4 recrystallized from ethyl acetate, isopropyl ether and nhexane   

                  TABLE 8                                                         ______________________________________                                         Ex.                                                                                ##STR51##                                                               No.  R.sup.1        q     Physical properties                                 ______________________________________                                        42                                                                                  ##STR52##     2     oil MS(m/z): 461(M.sup.+ +1) IRν.sub.max.sup.                              neat cm-1: 3280, 1735, 1650                         43                                                                                  ##STR53##     3     oil MS(m/z): 479(M.sup.+ +1) IRν.sub.max.sup.                              neat cm-1: 3380, 3280, 1735, 1650                   44   CH.sub.3       3     m.p. 147.5-149.5° C.*.sup.5                                            MS(m/z): 382(M.sup.+)                                                         IRν.sub.max.sup.nujol cm-1: 3280, 1715,                                    1650                                                45   (CH.sub.2).sub.3 CH.sub.3                                                                    3     m.p. 116-118° C.*.sup.5                                                FABMS(m/z): 425(M.sup.+ +1)                                                   IRν.sub.max.sup.nujol cm-1: 3350, 3180,                                    1740, 1650                                          ______________________________________                                         *.sup.5 recrystallized from methanolisopropyl ether (same as in the           following Examples)                                                      

EXAMPLE 46

A mixture of 1.45 g of methyl4-{[6-(2-thienyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-yl]acetylamino}benzoate,10 ml of methanol, 9 ml of a 2N aqueous sodium hydroxide solution and 4ml of tetrahydrofuran is stirred at room temperature overnight. Methanoland tetrahydrofuran are distilled off, and the residual mixture iswashed and acidified. The precipitated crystals are collected byfiltration, washed, dired and recrystallized from a mixture oftetrahydrofuran and isopropyl ether to give 1.33 g of4-{[6-(2-thienyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-yl]acetylamino}benzoicacid as colorless crystals.

Yield 94%

m.p. 250°-252° C.

FABMass(m/z): 471(M⁺ +1)

IR ν_(max) ^(nujol) (cm⁻¹): 3320, 3220, 1690, 1600

Sodium salt: colorless crystals

m.p. 267°-269° C. (decomp.)

FABMass(m/z): 515, 493(M⁺ +1)

IR ν_(max) ^(nujol) (cm⁻¹): 1680, 1600

EXAMPLES 47 TO 59

The corresponding starting compounds are treated in the same manner asdescribed in Example 46 to give the compounds shown in Tables 9 to 10.

                  TABLE 9                                                         ______________________________________                                         Ex.                                                                                ##STR54##                                                               No.  R.sup.1      q     Physical properties                                   ______________________________________                                        47                                                                                  ##STR55##   2     m.p. 151-154° C.*.sup.1 MS(m/z):                                       431(M.sup.+ +1) IRν.sub.max.sup.nujol cm-1:                                3320, 3180, 1710, 1660 Sodium salt: colorless                                 powder FABMS(m/z): 475, 453(M.sup.+ +1) IRν.sub                            .max.sup.nujol cm-1: 3270, 1650, 1570, 1160           48                                                                                  ##STR56##   3     m.p. 163.5-165° C.*.sup.6 MS(m/z):                                     465(M.sup.+ +1) IRν.sub.max.sup.nujol cm-1:                                3270, 1720, 1650, Sodium salt: pale yellow powder                             ABMS(m/z): 487(M.sup.+ +1) IRν.sub.max.sup.nujo                            l cm-1: 3270, 1630, 1560, 1150                        49                                                                                  ##STR57##   2     m.p. 171-172° C.*.sup.7 MS(m/z):                                       450(M.sup.+) IRν .sub.max.sup.nujol cm-1:                                  3350, 3160, 1705, 1655 Sodium salt: colorless                                 powder FABMS(m/z): 495, 473(M.sup.+ +1) IRν.sub                            .max.sup.nujol cm-1: 3260, 1640, 1570, 1460           50                                                                                  ##STR58##   1     m.p. 191-193.5° C.*.sup.6 MS(m/z):                                     436(M.sup.+) IRν.sub.max.sup.nujol cm-1: 3330,                             3160, 1720, 1660, 1150 Sodium salt: colorless                                 powder FABMS(m/z): 481, 459(M.sup.+ +1) IRν.sub                            .max.sup.nujol cm-1: 3280, 1600, 1160                 51                                                                                  ##STR59##   3     m.p. 113-115° C.*.sup.7 MS(m/z):                                       436(M.sup.+) IRν.sub.max.sup.nujol cm-1: 3340,                             3140, 1700, 1660 Sodium salt: colorless powder                                FABMS(m/z): 481, 459(M.sup.+ +1) IRν.sub.max.su                            p.nujol cm-1: 3200, 1645, 1550, 1400                  52                                                                                  ##STR60##   3     m.p. 142-144° C.*.sup.6 [α].sub.D.sup                            .20 +39.8°(c=3.71,  tetrahydrofuran)                                   Sodium salt: colorless powder [α].sub.D.sup.                            20 +44.3°(c=1.36, methanol)                    53                                                                                  ##STR61##   3     m.p. 143-144.5° C.*.sup.6 [α].sub.D.s                            up.20 -40.5°(c=2.42, tetrahydrofuran)                                  Sodium salt: colorless powder [α].sub.D.sup.                            20 -45.1°(c=1.02, methanol)                    54                                                                                  ##STR62##   2     m.p. 142.5-144° C.*.sup.7 [α].sub.D.s                            up.20 +46.5°(c=0.99, tetrahydrofuran)                                  Sodium salt: colorless prisms [α].sub.D.sup.                            20 +43.0°(c=2.72, methanol)                    55                                                                                  ##STR63##   2     m.p. 143-144.5° C.*.sup.7 [α].sub.D.s                            up.20 -46.2°(c=1.06, tetrahydrofuran)                                  Sodium salt: colorless prisms [α].sub.D.sup.                            20 -42.7°(c=2.67, methanol)                    ______________________________________                                         *.sup.6 recrystallized from tetrahydrofuranisopropyl ether                    *.sup.7 recrystallized from ethyl acetateisopropyl ether                 

                  TABLE 10                                                        ______________________________________                                         Ex.                                                                                ##STR64##                                                               No.  R.sup.1        q     Physical properties                                 ______________________________________                                        56                                                                                  ##STR65##     2     oil MS(m/z): 447(M.sup.+ +1) IRν.sub.max.sup.                              neat cm-1: 3260, 1720, 1650 Sodium salt:                                      amorphous FABMS(m/z): 491, 469(M.sup.+ +1)                                    IRν.sub.max.sup.nujol cm-1: 3260, 1650,                                    1595, 1580,                                         57                                                                                  ##STR66##     3     oil MS(m.z): 465(M.sup.+ +1) IRν.sub.max.sup.                              nujol cm-1: 3270, 1720, 1650 Sodium salt:                                     amorphous FABMS(m/z): 509, 487(M.sup.+ +1)                                    IRν.sub.max.sup.nujol cm.sup.-1 : 3260, 1650                               560                                                 58   CH.sub.3       3     m.p. 146-147.5° C.*.sup.5                                              IRν.sub.max.sup.nujol cm-1: 3310, 3270                                     1700, 1650                                                                    Sodium salt:                                                                  m.p. 210-212.5° C.*.sup.3                    59   (CH.sub.2).sub.3 CH.sub.3                                                                    3     m.p. 140-142.8° C.*.sup.8                                              MS(m/z): 410(M.sup.+)                                                         IRν.sub.max.sup.nujol cm-1: 3340, 3180,                                    1705, 1660, 1655                                                              Sodium salt:                                                                  m.p. 204-208° C.*.sup.9                      ______________________________________                                         *.sup.8 recrystallized from ethyl acetate                                     *.sup.9 recrystallized from isopropyl ether, isopropyl alcohol and water 

EXAMPLE 60

A mixture of 1.33 g of7-(3-pyridyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetic acid,20 ml of methylene chloride, 2 ml of thionyl chloride and one drop ofdimethyformamide is stirred at room temperature for 30 minutes. Afterthe solvent is distilled off, a solution of the resulting residue in 20ml of methylene chloride is added to a mixture of 2.5 ml of a 30%aqueous dimethylamine solution and 20 ml of methylene chloride undercooling, and the mixture is stirred for one hour. The organic layer isseparated from the mixture, washed, dried and evaporated to remove thesolvent to give 785 mg ofN,N-dimethyl-[7-(3-pyridyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-yl]acetamideas amorphous.

Yield 55%

FABMass(m/z): 374(M⁺ +1)

IR ν_(max) ^(nujol) (cm^(-l)): 3140, 1735, 1630

PREPARATION OF STARTING COMPOUNDS Preparation 1

(1) A solution of 5.4 g of oxalyl chloride in methylene chloride isadded dropwise to a suspension of 6.67 g of monoethylester of1,4-phenylenediacetic acid in methylene chloride under cooling andstirring. After one drop of dimethylformamide is added to the mixture,the mixture is stirred at room temperature for 3 hours and evaporated toremove the solvent. A solution of resulting yellow oil in methylenechloride is added dropwise to a suspension of 12.8 g of alminum chloridein methylene chloride under stirring at 0° C., and the mixture isstirred for 10 minutes. After ethylene gas is flowed into the mixturefor 30 minutes, the mixture is stirred at room temperature for 3 hours.Water and ethyl acetate are added to the mixture under cooling, and theorganic layer is separated therefrom, washed, dried and evaporated toremove the solvent.

The resulting residue is purified by silica gel column chromatography togive 5.67 g of ethyl 6-oxo-5,6,7,8-tetrahydronaphthalene-2-acetate ascolorless oil.

FABMass(m/z): 233(M⁺ +1)

IR ν_(max) ^(neat) (cm⁻¹): 1730-1720

(2) A solution of 6.36 g of the product obtained above, 9.5 ml ofpyridine and 4.33 g of methoxylamine hydrochloride in methanol isrefluxed for 2.5 hours under argon. After the solvent is distilled off,ethyl acetate and 10% hydrochloric acid are added to the residue. Theorganic layer is separated from the mixture, washed, dried andevaporated to remove the solvent. The resiual oil is purified by silicagel column chromatography to give 5.37 g of ethyl6-methoxyimino-5,6,7,8-tetrahydronaphthalene-2-acetate as pale yellowoil.

Mass(m/z): 261(M⁺)

IR ν_(max) ^(neat) (cm⁻¹): 1735, 1050

(3) 216 mg of platinum oxide (IV) and 540 mg of oxalic acid are added toa solution of 1.57 g of the product obtained above in ethanol, and themixture is subjected to catalytic hydrogenation under hydrogen gasatmosphere (2 to 3 atm) overnight. After a solution of hydrogen chloridein ethanol is added to the mixture, the catalyst is filtered off. Afterthe solvent is distilled off, the residue is recrystallied from amixture of ethanol and ether to give 772 mg of ethyl6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate hydrochloride as palebrown prism.

m.p. 217°-221° C. (decomp.)

PREPARATION 2

5.5 ml of 2M borane-methylsulfide complex in tetrahydrofuran are addedto a solution of 1.31 g of ethyl6-methoxyimino-5,6,7,8-tetrahydronaphthalene-2-acetate intetrahydrofuran under argon at -5° to 0° C., and the mixture is stirredat room temperature overnight. Ethanol and 9% hydrogen chloride-ethanolare added to the mixture under cooing and stirring, and the mixture isstirred at room temperature for 30 minutes. After the solvent isdistilled off, the residue is crystallized with a mixture of ethanol andether to give 990 mg of2-(6-amino-5,6,7,8-tetrahydronaphthalene-2-yl)ethanol hydrochloride ascolorless solid.

m.p. 221°-224° C. (decomp.)

Preparation 3

(1) 110.52 g of trifluoroacetic anhydride are added dropwise to asolution of 76.29 g of DL-N-(methoxycarbonyl)aspartic acid in ethylacetate under cooling. After the mixturte is stirred at room temperaturefor 2 hours, a part of solvent is distilled off. n-hexane is added tothe solution slowly under cooling, and the precipitated crystals arecollected by filteration to give 65.54 g ofDL-N-(methoxycarbonyl)aspartic anhydride as colorless prism.

m.p. 102°-103° C.

(2) A mixture of 117.4 g of the product obtained above, 226.3 g ofalminum chloride, 10.4 g of nitromethane and 270 g of benzene isrefluxed for 3 hours. 10% hydrochloric acid is added to the reactionmixture, ethyl acetate and tetrahydrofuran are added thereto. Theorganic layer is separated from the mixture, dried and evaporated toremove the solvent. The residual solids, after the treatment ofcharcoal, are recrystallized from a mixture of ethyl acetate andn-hexane to give 147.9 g of 4-oxo-4-phenyl-2-methoxycarbonylaminobutyricacid as colorless prism.

m.p. 132°-135° C.

(3) A suspension of 25.12 g of the product obtained above, 52.5 ml of 2Nhydrochloric acid and 2.60 g of palladium-carbon in tetrahydrofuran issubjected to catalytic hydrogenation under hydrogen gas atmosphere (4atm) for 10 hours. After the reaction, the catalyst is filtered off, anda part of solvent is distilled off. Ethyl acetate is added to thesolution, the solution is washed, dried and a part of solvent isdistilled off. n-hexane is added to the mixture and the precipitatedcrystals are collected by filtration to give 22.07 g of4-phenyl-2-methoxycarbonylaminobutyric acid as colorless needles.

m.p. 108.5°-110° C.

(4) A solution of 51.28 g of the product obtained above, 96.9 g of2,2,2-trichloroethanol and 10.28 g of p-toluenesulfonic acid monohydratein toluene is refluxed with Dean Strak apparatus for 5 hours. Thereaction mixture is washed, dried and evaporated to remove the solvent,and the residue is distilled to give 71.5 g of 2,2,2-trichloroethyl4-phenyl-2-methoxycarbonylaminobutyrate.

b.p. 90° to 95° C. (0.6 mmHg)

The product is allowed to stand to give colorless needles.

m.p. 31°-35° C.

(5) A solution of 1.77 g of ethyl 2-chloro-2-methylthioacetate inmethylene chloride and a solution of 5.22 g of tin chloride (IV) inmethylene chloride are added dropwise to 3.69 g of the product obtainedabove at the same time under cooling and stirring. After the mixture isstirred at room temperature for 2 hours, water, chloroform and then 10%hydrochloric acid are added thereto. The organic layer is separated fromthe mixture, dried and evaporated to remove the solvent. The residue ispurified by silica gel column chromatography to give 4.37 g of ethyl2-{4-[3methoxycarbonylamino-3-(2,2,2-trichloroethoxycarbonyl)propyl]phenyl}-2-methylthioacetateas colorless oil.

IR ν_(max) ^(neat) (cm⁻¹): 3348, 1763, 1732

(6) A mixture of 1.81 g of the product obtained above, 475 mg of zinkpowder and 15 ml of acetic acid is stirred at room temperature for 30minutes, and then refluxed for one hour.

475 mg of zink powder are added to the mixture, and the mixture isrefluxed for 1.5 hour. Further 950 mg of zink powder are added to themixture and the mixture is refluxed for 2 hours. Insoluble materials arefiltered off, and the filtrate are condensed. The residue is extractedwith ethyl acetate, washed, dried and evaporated to remove the solvent.The residue is purified by silica gel column chromatography, andrecrystallized from a mixture of ethyl acetate and n-hexane to give 956mg of ethyl 4-(3-carboxy-3-methoxycarbonylaminopropyl)phenylacetate.

m.p. 108°-110° C.

(7) A solution of 1.62 g of the product obtained above, 0.66 ml ofoxalyl chloride and a catalytic amount of dimethylformamide in methylenechloride is stirred under cooling for 5 minutes and then at roomtemperature for 3 hours. 2.68 g of alminum chloride are added to themixture, and the mixture is stirred under cooling for one hour. Waterand ethyl acetate are added to the mixture, and the organic layer isseparated therefrom, washed, dried and evaporated to remove the solvent.The resulting oil is purified by silica gel column chromatography, andrecrystallized from a mixture of ethyl acetate and n-hexane to give 983mg of ethyl8-oxo-7-methoxycarbonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate ascolorless needles.

m.p. 95°-97° C.

(8) A suspension of 0.92 g of the product obtained above, 60 mg ofsodium borohydride in methanol is stirred under cooling for 10 minutes.After the solvent is distilled off, ethyl acetate and water are addedthereto. The organic layer is separated from the mixture, washed, driedand evaporated to remove the solvent. The resulting crystals arerecrystallized from a mixture of ethyl acetate and n-hexane to give 700mg of ethyl8-hydroxy-7-methoxycarbonylamino-5,6,7,8-tetrahydronaphthalene-2-acetateas colorless prism.

m.p. 99°-100.5° C.

(9) A suspension of 615 mg of the product obtained above, 180 mg ofoxalic acid and 100 mg of 10% palladium-carbon in ethanol is subjectedto catalytic hydrogenation under hydrogen gas atmosphere (4 atm) at 50°C. for 16 hours. The catalyst is filtered off, and the filtrate iscondensed. Water is added to the residue and the solution is extractedwith ethyl acetate, and the extract is washed, dried and evaporated toremove the solvent. The residue is recrystallized from a mixture oftoluene and n-hexane to give 500 mg of ethyl7-methoxycarbonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate.

m.p. 89°-90° C.

(10) A solution of 586 mg of the product obtained above in 6Nhydrochloric acid is refluxed for 13 hours. After the solvent isdistilled off, 10% hydrogen chloride-methanol and methanol are added tothe residue. The mixture is refluxed for 4 hours, and the solvent isdistilled off. The residue is recrystallized from a mixture of methanoland ether to give 486 mg of methyl7-amino-5,6,7,8-tetrahydronaphthalene-2-acetate hydrochloride ascolorless needles.

m.p. 158°-161.5° C.

Concomitantly, ethyl8-oxo-7-methoxycarbonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate istreated in the same manner as described in (9) to give ethyl7-methoxycarbonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate.

What is claimed is:
 1. An aminotetrahydronaphthalene derivative of theformula: ##STR67## wherein R² is hydroxymethyl group, carboxyl group, alower alkoxycarbonyl group or a group of the formula: ##STR68## whereinR³ is hydrogen atom or a lower alkyl group, R⁴ is a loweralkoxycarbonyl-lower alkyl group or carboxy-lower alkyl group, and m andn are different and are 1 or 2, or a mineral or organic acid saltthereof.
 2. An aminotetrahydronaphthalene derivative which is: ethyl6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate, or a mineral or organicacid salt thereof;2-(6-amino-5,6,7,8-tetrahydronaphthalene-2-yl)ethanol, or a mineral ororganic acid salt thereof; or methyl7-amino-5,6,7,8-tetrahydronaphthalene-2-acetate, or a mineral or organicacid salt thereof.